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Published on: October 12, 2017
S-Adenosylhomocysteine: a better indicator of vascular disease than homocysteine?
1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. conrad.wagner@vanderbilt.edu
Insights
Measuring plasma S-adenosylhomocysteine (AdoHcy) offers a more sensitive indicator for vascular disease than homocysteine. A new rapid immunoassay makes AdoHcy measurement accessible for general use in large studies.
Area of Science:
- Biochemistry
- Cardiovascular Medicine
- Metabolomics
Background:
- Elevated plasma total homocysteine is a known risk factor for vascular disease, but the underlying pathophysiology remains unclear.
- S-adenosylhomocysteine (AdoHcy) is the metabolic precursor to homocysteine and is present in plasma at much lower concentrations, posing measurement challenges.
- Traditional methods for AdoHcy measurement are complex and time-consuming, limiting its use in large-scale studies.
Purpose of the Study:
- To introduce a rapid immunoassay for measuring plasma AdoHcy.
- To highlight the advantages of plasma AdoHcy measurement over plasma homocysteine for vascular disease risk assessment.
- To facilitate broader clinical and research applications of AdoHcy as a biomarker.
Main Methods:
- Development and validation of a rapid immunoassay for human plasma S-adenosylhomocysteine (AdoHcy).
- Comparison of AdoHcy and homocysteine levels in patient and control groups.
- Evaluation of AdoHcy's sensitivity as a vascular disease indicator.
Main Results:
- A novel, rapid immunoassay for plasma AdoHcy is now available for general use.
- Plasma AdoHcy measurement shows a smaller overlap between control and patient values compared to homocysteine.
- Higher plasma AdoHcy concentrations are a more sensitive indicator of vascular disease than elevated homocysteine levels.
Conclusions:
- Plasma AdoHcy measurement is a more sensitive biomarker for vascular disease risk.
- The new immunoassay simplifies AdoHcy detection, enabling wider clinical application.
- Understanding AdoHcy's role in methyltransferase inhibition provides a mechanistic link to vascular pathophysiology.
Abstract:
It is widely accepted that elevated plasma total homocysteine is an independent risk factor for vascular disease. The relation is believed to be causal, but there is no generally accepted mechanism for the pathophysiology involved. The metabolic precursor of homocysteine in all tissues is S-adenosylhomocysteine (AdoHcy). AdoHcy is present in normal human plasma at concentrations approximately 1-500th of those of homocysteine, a fact that presents difficulties in measurement. The requirement for specialized equipment, complicated time-consuming methodology, or both is a reason that measurement of plasma AdoHcy has not generally been carried out in large studies. A recently published rapid immunoassay for AdoHcy in human plasma should make measurement of this important metabolite available for general use. Advantages of the measurement of plasma AdoHcy include 1) a smaller overlap of values between control subjects and patients, and thus the possibility of observing significant differences in fewer samples, 2) an accepted mechanism of metabolic activity as an inhibitor of all S-adenosylmethionine-mediated methyltransferases, and 3) evidence (from recent studies) that a higher plasma concentration of AdoHcy is a more sensitive indicator of vascular disease than is a higher plasma concentration of homocysteine.
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